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Lateral assembly of the immunoglobulin protein SynCAM 1 controls its adhesive function and instructs synapse formation
Synapses are specialized adhesion sites between neurons that are connected by protein complexes spanning the synaptic cleft. These trans ‐synaptic interactions can organize synapse formation, but their macromolecular properties and effects on synaptic morphology remain incompletely understood. Here,...
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Published in: | The EMBO journal 2011-11, Vol.30 (23), p.4728-4738 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | Synapses are specialized adhesion sites between neurons that are connected by protein complexes spanning the synaptic cleft. These
trans
‐synaptic interactions can organize synapse formation, but their macromolecular properties and effects on synaptic morphology remain incompletely understood. Here, we demonstrate that the synaptic cell adhesion molecule SynCAM 1 self‐assembles laterally via its extracellular, membrane‐proximal immunoglobulin (Ig) domains 2 and 3. This
cis
oligomerization generates SynCAM oligomers with increased adhesive capacity and instructs the interactions of this molecule across the nascent and mature synaptic cleft. In immature neurons,
cis
assembly promotes the adhesive clustering of SynCAM 1 at new axo‐dendritic contacts. Interfering with the lateral self‐assembly of SynCAM 1 in differentiating neurons strongly impairs its synaptogenic activity. At later stages, the lateral oligomerization of SynCAM 1 restricts synaptic size, indicating that this adhesion molecule contributes to the structural organization of synapses. These results support that lateral interactions assemble SynCAM complexes within the synaptic cleft to promote synapse induction and modulate their structure. These findings provide novel insights into synapse development and the adhesive mechanisms of Ig superfamily members.
SynCAM 1 is a neuronal homo‐ and heterophilic cell adhesion molecule. This study shows that
cis
oligomerization of SynCAM 1 promotes cell adhesion and contributes to the formation and organization of synaptic adhesion sites. |
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ISSN: | 0261-4189 1460-2075 |
DOI: | 10.1038/emboj.2011.336 |